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Liquid atomization plays an important role in the manufacturing of the pharmaceutical products. It is used in all production steps where liquid is applied. In some productions steps precise control over spraying parameters is essential. These steps include fluid bed granulation, film coating of tablets and pellet coating. Precise atomization of liquids enables control over the granule formation in granulation steps and film formation in coating steps. Atomization process includes breakup of liquid and formation of droplets, which is a complex and important phenomenon that should be carefully evaluated for each particular use. This study focuses on characterization of atomization process by the means of combining high-speed imaging, optical microscopy and continuous backlight illumination together with robust image processing algorithm. With pure water and three different hypromellose (HPMC) polymer dispersions that are frequently used for film coating of solid dosage forms, we successfully measured mean droplet size (Sauter mean diameter between 49 and 413 μm), droplet size distribution and droplet speed (in average 10–46 m/s). It was shown that the shape of cumulative volumetric droplet size distribution can be used to evaluate the successfulness of ligament breakup (i.e., formation of droplets) and by that the spray quality. Moreover, the obtained trends and empirical correlations between droplet size and other process parameters are useful in practice in order to select appropriate settings for optimal coating process parameters. Due to the simplicity of proposed method and data processing, the entire system is potentially suitable for near real-time coating monitoring and for rapid optimization of the atomization process.

Fused deposition modelling (FDM) is the most explored three-dimensional (3D) printing technique in pharmaceutics. However, there is still a lack of knowledge about the factors influencing the properties of the printed forms. Here, the main and combined effects of the presence of a pore former (mannitol, 0% or 10%), the infill percentage (50% or 100%) and the drug percentage (5% or 10%) on the pharmaceutical properties of 3D-printed forms were evaluated by a design of experiments (DoE) approach. Poly(Ɛ-caprolactone) filaments were produced by hot-melt extrusion and dexamethasone was used as a hydrophobic model drug. The 23 factorial design afforded eight formulations printed at 105 °C. The drug content ranged from 9.87 to 25.59 mg/unit, depending on the drug and infill percentages. The drug release profiles followed the Higuchi model. The infill percentage modulated the drug release rate, whereas the pore former had a combined effect on this parameter, depending on the drug and infill percentage levels. According to the DoE data, besides the changes in the infill percentage, the addition of a pore former can also tailor the drug release rate from 3D-printed solid forms. These findings may assist the development of personalised tumour implants by 3D printing.

Layer weight control, delamination and cross-contamination are major challenges in the production of compacted multilayer tablets (MLT). In this work, we describe a novel approach to manufacturing MLT: the Gluing Pills Technology (GPT). High loads of ibuprofen free acid and caffeine anhydrate were blended with microcrystalline cellulose (MCC) and dibasic calcium phosphate dihydrate (DCPD) and compacted into monolayer tablets. They were glued together via the GPT using solutions of either fish gelatin or polyvinylpyrrolidone K90 as gluing agents with defined viscosity. Factors that have a substantial impact on the deformation behavior of blends (i.e., elastic recovery, tensile strength and porosity) of monolayer tablets were investigated in terms of bilayer tablets manufactured via the GPT. The results indicated that high levels of elastic recovery negatively affected the robustness of GPT bilayer tablets and that the type of gluing agent was critical. Raman microscopy analysis was successfully applied to qualitatively assess the function of gluing layer as a barrier to cross-contamination between two monolayer tablets. This study shows the feasibility of the GPT for manufacturing of robust MLT, emphasizing its potential in terms of real-time production of individualized fixed-dose combinations and application in both translational pharmaceutics and personalized medicine.

Essential oils are recognized as valuable active pharmaceutical ingredients attributed to a set of biological properties, which include antibacterial, antifungal, antiviral, antioxidant, anticancer, immune-modulatory, analgesic and anti-inflammatory activities. Their use in pharmaceutics is however compromised by their limited water solubility and low physicochemical stability (i.e. volatility, oxidation). In order to overcome these limitations, we aimed to develop nanostructured lipid carriers (NLC) as delivery systems for Mediterranean essential oils, in particular Rosmarinus officinalis L., Lavandula x intermedia "Sumian", Origanum vulgare subsp. hirtum and Thymus capitatus essential oils, selected on the basis of their antioxidant and anti-inflammatory activities. NLC composed of Softisan (as solid lipid) have been produced by phase inversion temperature (PIT) and high-pressure homogenization (HPH), using two different emulsifiers systems. Particles have been further characterized for their mean particle size, polydispersity, zeta potential, morphology and chemical interactions. Best NLC formulations were obtained with Kolliphor/Labrafil as surfactants, and using Rosmarinus, Lavandula and Origanum as essential oils (PDI between 0.126 and 0.141, Zave 200 nm). Accelerated stability studies have also been carried out to estimate the effect of the production method and surfactant composition on the long-term stability of EOs-loaded NLC. In vitro biological cell viability and anti-inflammatory activities were evaluated in Raw 264.7 cells (macrophage cell line), while in vitro antioxidant activity was checked by DPPH assay. Lavandula and Rosmarinus NLC were shown to be the most biocompatible formulations up to a concentration of 0.1% (v/v), whereas they were able to induce a dose-dependent anti-inflammatory activity in the order Lavandula Rosmarinus ≥ Origanum.

Five commercially available starches modified with octenyl succinic anhydride (OSA) are characterized at a molecular, physicochemical and bulk level providing useful data for designing pharmaceutical products. The degree of substitution (DS) of the starches range from 0.017 to 0.032 and their molecular weights (Mw) and radius of gyration (Rz) are lower than those of native starch, suggesting additional modification processes besides the chemical treatment with OSA. The ability of the starches to reduce the water surface tension keeps a direct relationship with the DS and an inverse association with the Mw. Thermal properties, crystallinity assays and morphology evidence that most modified starches characterize by amorphous aggregated structures, possibly generated by gelatinization processes, which favor the flow properties of the powders. Water sorption and surface energy behaviors seem to be related to the number of octenyl succinate (OS) moieties. After dispersion in water, shear-thinning and Newtonian behaviors also depend on the type of OS-starch.

Many pharmaceuticals such as pills, capsules, or tablets are prepared in a dried and powdered form. In this field, spray drying plays a critical role to convert liquid pharmaceutical formulations into powders. In addition, in many cases it is necessary to encapsulate bioactive drugs into wall materials to protect them against harsh process and environmental conditions, as well as to deliver the drug to the right place and at the correct time within the body. Thus, spray drying is a common process used for encapsulation of pharmaceuticals. In view of the rapid progress of nanoencapsulation techniques in pharmaceutics, nano spray drying is used to improve drug formulation and delivery. The nano spray dryer developed in the recent years provides ultrafine powders at nanoscale and high product yields. In this paper, after explaining the concept of nano spray drying and understanding the key elements of the equipment, the influence of the process parameters on the final powders properties, like particle size, morphology, encapsulation efficiency, drug loading and release, will be discussed. Then, numerous application examples are reviewed for nano spray drying and encapsulation of various drugs in the early stages of product development along with a brief overview of the obtained results and characterization techniques.

The discovery of new intravenous drug delivery carrier for water-insoluble drug is a challenging task. In this paper, novel two-vial formulation of paclitaxel (PTX)-loaded lipid nanoemulsions (TPLEs) with particle sizes of 110nm (TPLE-1), 220nm (TPLE-2) and 380nm (TPLE-3), which were formed by mixing a PEG400 solution of PTX and 10% (w/w) blank lipid emulsions (BLEs) with different particle size prior to use, were developed and comparatively evaluated for their pharmaceutics, pharmacokinetics, biodistribution, in vitro and in vivo anticancer efficiency. Among them, TPLE-1 displayed higher PTX-loading, slower PTX-release and larger PTX-distribution in oil-phase, significantly reduced extraction by RES organs, increased tumor-uptake, showed stronger cytotoxicity against MCF-7 cells and more potent anticancer efficacy on MCF-7 tumor-bearing nude mice, and had greater plasma AUC0-∞ value, smaller plasma clearance (CL), longer mean residence time (MRT) and elimination half-life (T1/2) in SD rats. It also exhibited the same in vivo efficacy as Taxol® and even produced less hemolysis and intravenous irritation. Moreover, its LD50 was 4.3-fold higher than that of Taxol®. All results demonstrate that TPLE-1 is a promising candidate drug due to its high tumor-accumulation and effectiveness, low toxicity, good safety and druggability in clinical application for the cancer therapy.

Resveratrol (RVT) is one of the potent anticancer phytochemicals which has shown promising potential for breast cancer therapy. However, its short half-life and low bioavailability is a major hurdle in its effective use. In this study, we have developed nanostructured lipid carriers (NLCs) of RVT to enable localized delivery of the drug to the breast tissues using microneedle arrays to improve effectiveness. The NLCs were optimized using the Design of Experiments approach and characterized for their particle size, polydispersity index, zeta potential and entrapment efficiency. The RVT-NLCs delivered using microneedle array 1200 showed a higher permeation of RVT across the skin with lower skin retention compared to pure RVT. Further, RVT-NLCs showed higher anticancer activity on MDA-MB-231 breast cancer cell lines and enhanced internalization compared to pure RVT. Moreover, the RVT-NLCs were found to inhibit the migration of MDA-MB-231 breast cancer cell lines. Preclinical studies in rats showed that RVT-NLCs delivered via microneedles demonstrated a remarkable increase in the Cmax, Tmax and AUC0-inf, and a higher localization in breast tissue compared to pure RVT administered orally. These results suggests that the RVT-NLCs administered by microneedle array system is an effective strategy for the local delivery of RVT for breast cancer therapy Refereed/Peer-reviewed

When applied to skin, particulate matter has been shown to accumulate in hair follicles. In addition to follicles, the skin topography also incorporates trench-like furrows where particles potentially can accumulate; however, the furrows have not been as thoroughly investigated in a drug delivery perspective. Depending on body site, the combined follicle orifices cover up to 10% of the skin surface, while furrows can easily cover 20%, reaching depths exceeding 25 µm. Hence, porous particles of appropriate size and porosity could serve as carriers for drugs to be released in the follicles prior to local or systemic absorption. In this paper, we combine multiphoton microscopy, scanning electron microscopy, and Franz cell diffusion technology to investigate ex-vivo skin accumulation of mesoporous silica particles (average size of 400–600 nm, 2, and 7 µm, respectively), and the potential of which as vehicles for topical delivery of the broad-spectrum antibiotic metronidazole. We detected smaller particles (400–600 nm) in furrows at depths of about 25 µm, also after rinsing, while larger particles (7 µm) where located more superficially on the skin. This implies that appropriately sized porous particles may serve as valuable excipients in optimizing bioavailability of topical formulations. This work highlights the potential of skin furrows for topical drug delivery.

Three-dimensional printing (3DP) technology offers unique advantages for pharmaceutical applications. However, most of current 3D printing methods and instrumentations are not specifically designed and developed for pharmaceutical applications. To meet the needs in pharmaceutical applications for precision, compatibility with a wide range of pharmaceutical excipients and drug materials without additional processing, high throughput and GMP compliance, an extrusion-based 3D printer based on Melt Extrusion Deposition (MED™) 3D printing technology was developed in this study. This technology can process powder pharmaceutical excipients and drugs directly without the need of preparing filament as required by FDM 3D printing. Six different tablet designs based on compartment models were used to demonstrate the precision and reproducibility of this technology. The designed tablets were fabricated using the GMP-compliant MED™ 3D printer and were evaluated in vitro for drug release and in vivo for selected designs using male beagle dogs. Tablet designs with one or more compartments showed versatile release characteristics in modulating the release onset time, release kinetics, duration of release and mode of release. Multiple drugs or formulations were fabricated into a single tablet to achieve independent release kinetics for each drug or to fine-tune the pharmacokinetic profile of a drug. Building upon the theoretical analysis of models, precision and reproducibility of MED™ 3D printing technology, a novel product development approach, 3D printing formulation by design (3DPFbD®) was developed to provide an efficient tool for fast and efficient pharmaceutical product development. The MED™ 3D printing represents a novel and promising technology platform encompassing design and development of modified drug release products and has potential to impact the drug delivery and pharmaceutical product development.

Despite the increasing interest in pharmaceutical use of mesoporous silica, there is still only limited knowledge on mechanisms of pore loading and subsequent drug desorption and release. Hence the aim of this work was to address the mechanistic aspects of drug loading into the mesoporous silica pores and to minimise the risk of pore clogging. Hydrophilic solvents (polysorbate 20 and polyethylene glycol 200) with high dissolving capacity for the model drug celecoxib were studied for their surface tension as well as dynamic viscosity by considering hydration. As an innovation in liquisolid systems preparation, a rather simple drug loading method on a mesoporous carrier was introduced by using semi-volatile solvent mixtures. Fast liquid loading into the pores was achieved due to the lowered viscosity and surface tension of the whole solvent system. Drug release kinetics suggested that lipid-based formulations belonging to class IV of Lipid Formulation Classification System may exhibit a lower risk of incomplete desorption from a carrier. The utilisation of volatile solvents during preparation had no negative impact on the liquisolid systems' dissolution behaviour. All prepared formulations showed similar significantly faster dissolution profiles compared to the physical mixture. The novel approach has potential to promote liquisolid applications in pharmaceutics.

One of the main tasks of modern pharmaceutics is enhancing the solubility of drugs. The approaches for solving this problem include producing active pharmaceutical ingredients in the amorphous state. However, the use of amorphous drugs requires the determination of their kinetic stability. The latter is often assessed using isothermal techniques, which are time-consuming. Alternatively, non-isothermal methods can be employed, allowing to determine the kinetic triplet more rapidly. Also, such techniques can be used to develop predictive models for storage stability. The production of the amorphous state itself typically requires fast cooling rates, which may not be easily accessible. Fast scanning calorimetry is a promising tool for the investigation of amorphous drug systems. In the present work, the crystallization of the model drug dipyridamole was investigated using the fast scanning calorimetry method. The kinetic stability of the amorphous form of the drug was evaluated using both, isothermal and non-isothermal methods. The Nakamura crystallization model was found to be applicable for the prediction of the temporal stability of the amorphous drug forms. The obtained results may find applications in the investigation of the kinetic stability of amorphous drug systems.

Modified-release oral dosage forms are commonly used in pharmaceutics to delay or sustain the release of drugs. Nowadays, they are only marketed as solid dosage forms such as capsules or tablets. Therefore, the development of a liquid oral dosage form with modified-release properties has been keenly awaited to increase the compliance of patients with a swallowing impairment, such as paediatric, older or critically ill patients. In this study, a new technology has been developed that consists of multi-layered particles suspended extemporaneously in a syrup, using omeprazole as a model drug. The coating procedure was optimized to obtain a yield of minimum 90% w/w and a mean diameter below 500 µm. Eudragit® E100 and Eudragit® L100-55 were used to prevent the early release of omeprazole in the syrup and in the acidic environment of the stomach, respectively. These polymers allowed the stability of the coated particles to be ensured when dispersed in a liquid and the enteric release of the drug to be targeted. It was demonstrated that our new system presented similar release performances to existing marketed enteric dosage forms. It is able to protect omeprazole for 2 h in acidic medium at pH 1.2, while omeprazole was entirely released at pH 6.8 within 45 min. Once the final suspension is prepared extemporaneously, it presents sufficient stability to guarantee the administration of multiple doses filled into a syrup bottle and kept for a limited storage time at room temperature (e.g. up to 10 doses to be administered within 10 days).

Formulation of poorly water-soluble drugs with mesoporous silica has become a thriving field of pharmaceutics. The theoretical critical pore diameter has been introduced as a maximum value below which an undesired drug crystallization is suppressed by spatial confinement. Currently, only few values have been reported and study of fast crystallising drugs is missing especially at relevant storage temperatures. This study investigated the critical pore diameter of three model drugs with a poor glass-forming ability (i.e. haloperidol, carbamazepine and benzamide) using different mesoporous carriers (Parteck® SLC 500, Neusilin® US2, Syloid® XDP 3050 and Aeroperl® 300 Pharma) and subsequently monitored physical formulation stability over three months by X-ray powder diffraction. The selected drugs showed clear differences in their estimated critical pore diameters, whereas a temperature dependence was barely relevant for pharmaceutical storage conditions. Superior stability was noted for the formulations containing benzamide in line with its predicted relatively large critical pore diameter of 29.5 nm. Contrarily, impaired physical stability depending on drug loading was observed in the case of haloperidol representing a compound with a rather small critical pore diameter (8.4 nm). These findings confirm the importance of estimating the critical pore diameter, especially for poor glass-forming drugs.

Multimodal therapeutic approach has been gaining lot of attention for effective therapy of cancer. In the present work, a novel and unique pH responsive nanoplatform have been developed for multimodal therapy of glioblastoma using protein, biopolymer and MOFs. Lactoferrin (Lf) has been used as protein matrix for loading titanocene which was then enclosed in ZIF-8 framework along with 5-FU (ZIF-8@Lf-TC). The ZIF-8 was further coated with Lenalidomide-HA conjugate linked via hydrazone linkage (LND-HA@ZIF-8@Lf-TC). The developed nanocomposite was extensively characterized using spectroscopic, x-ray and electron microscopic techniques. The nanocomposites were evaluated for pH responsive drug release, stability, bio-interaction, and haemocompatibility which confirmed pH responsive nature of nanocomposite, stability and absence of any significant interaction with biomolecules. In obtained results for in vitro cell line studies performed in U87MG and RAW264.7 cells demonstrated enhanced cell cytotoxicity against cancer cells which was further supported by results of cellular ROS generation and surface ROS generation by nanocomposites. The Zinc and Lf mediated disruption of intracellular IL-6 and TNFα levels was observed with synthesized nanocomposites. They demonstrated pH responsive release of 5-FU and LND along with sustained release of both drugs in simulated medium. The LND-HA@ZIF-8@Lf-TC demonstrated superior cell growth supressing ability compared to ZIF-8@Lf-TC and ZIF-8. The nanocomposites were stable in biomimicking environment as well as did not show any significant interaction with RBC, plasma or CSF. The overall results suggest that LND-HA@ZIF-8@Lf-TC can be explored as promising platform for dual drug delivery mediated multimodal therapy of cancer.

The central nervous system (CNS) is a vital part of human body which coordinate the actions by transmitting signals. Because of the existence of the blood-brain barrier and the blood-spinal cord barrier, diseases in CNS can hardly be directly intervened by non-invasive methods. While systemic delivery usually requires extravagant drug dosage and leads into toxicity in unexpected tissues, local drug delivery in CNS tissues provides a solution for the problems of physiological barriers and systematic side effects. Biomaterials are applied in local drug delivery system (LDDS) for CNS disease therapy with aims of tuning the drug release property and improving bioavailability, solubility, stability and safety of pharmaceutics. The indispensable importance and distinct physiological structure of cerebrospinal area bring about challenges to biomaterials in LDDS. Thus, properties of drug delivery systems are necessitated with prudently concern. In this review, the development of LDDS utilizing biomaterials will be presented, including sustained release, local parameter-responsible release, and regional cell-selective active targeting release. Studies on biomaterials employed as pharmaceuticals will give rise to a more efficacious method and the better understanding of LDDS design in CNS.

Saxagliptin (SAX) is a dipeptidyl peptidase-4 enzyme inhibitor molecule now explored for its activity in the therapy of Alzheimer's disease. Being extremely hydrophilic, it is unable to permeate the blood-brain barrier by the conventional therapy modalities. Further repurposing the drug, SAX is associated with a reduction in the blood sugar level in the periphery. In the present study, the chitosan-l-valine conjugate was synthesized by carbodiimide chemistry. The conjugate was then used to prepare nanoparticles encapsulating SAX. The nanoparticles were characterized by particle size, surface morphology, and entrapment efficiency. The stability of the formulations was determined by incubation with rat plasma and brain homogenate. The blood brain barrier permeability of the nanoparticles was successfully demonstrated by the incorporation of fluorescent dye, Rhodamine B in the nanoparticles. In vivo studies were conducted in rats and the results showed that the nanoparticles were highly stable in the plasma releasing only a minute amount of SAX (2.5 ng/mL) which was less than the Cmax of the pure SAX (51 ng/mL). The brain uptake studies showed an accumulation of 53 ng/mL SAX from the nanoparticles whereas the pure SAX showed no detectable amount of the drug after 24 h. The pharmacokinetic studies demonstrated that nanoparticles had an (AUC0-t) of 3.42 times lower than the pure SAX, indicating the stability of the prepared formulation in the plasma.

Kaolinite Al2Si2O5(OH)4 is an abundant and inexpensive geomaterial regarded as one of the most common clay minerals in the earth's crust and the most widespread phase among the other kaolin polymorphs (halloysite, dickite and nacrite). Structurally, it is a hydrous aluminum phyllosilicate member belonging to the dioctahedral 1:1 kaolin mineral group. The particle size of the pseudohexagonal kaolinite platelets is normally

The aim of this study was to determine the individual and combined effects of peptide dendrimers and low frequency ultrasound on the transdermal permeation of ketoprofen. Arginine terminated peptide dendrimers of varying charges (4+, 8+ and 16+, named as A4. A8 and A16 respectively) were synthesized and characterized. Ketoprofen was subjected to passive, peptide dendrimer-assisted and sonophoretic permeation studies (with and without dendrimer application) across Swiss albino mouse skin, both in vitro and in vivo. The studies revealed that the synthesized peptide dendrimers considerably increased the transdermal permeation of ketoprofen and displayed enhancement ratios of up to 3.25 (with A16 dendrimer), compared to passive diffusion of drug alone in vitro. Moreover, the combination of peptide dendrimer treatment and ultrasound application worked in synergy and gave enhancement ratios of up to 1369.15 (with ketoprofen-A16 dendrimer complex). In vivo studies demonstrated that dendrimer and ultrasound-assisted permeation of drug achieved much higher plasma concentration of drug, compared to passive diffusion. Comparison of transdermal and oral absorption studies revealed that transdermal administration of ketoprofen with A8 dendrimer showed comparable absorption and plasma drug levels with oral route. The excised mouse skin after in vivo permeation study with dendrimers and ultrasound did not show major toxic reactions. This study demonstrates that arginine terminated peptide dendrimers combined with sonophoresis can effectively improve the transdermal permeation of ketoprofen.

In order to increase the solubility of poorly water-soluble natural product, xanthoceraside, an effective anti-AD compound from Xanthoceras sorbifolia Bunge, and maintain its natural property, the xanthoceraside hollow gold nanoparticles were successively prepared by green ultrasonic method with silica spheres as templates and HF solution as selective etching solvent. Hollow gold nanoparticles and drug-loaded hollow gold nanoparticles were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and differential scanning calorimetry (DSC). The solubilities of xanthoceraside loaded on hollow gold nanoparticles were increased obviously from 3.0μg/ml and 2.5μg/ml to 12.7μg/ml and 10.7μg/ml at 25°C and 37°C, respectively. The results of XRD and DSC indicated that the reason for this increase was mainly due to the amorphous state of xanthoceraside loaded on the hollow gold nanoparticles. In summary, the method of loading xanthoceraside onto hollow gold nanoparticles was a green and useful strategy to improve the solubility and dissolution of poorly water-soluble natural products and worth to applying to other natural products.

Emulsions are widely used in pharmaceutics for the encapsulation, solubilization, entrapment, and controlled delivery of active ingredients. In order to answer the increasing demand for clean label excipients, natural polymers can replace the potentially irritative synthetic surfactants used in emulsion formulation. Indeed, biopolymers are currently used in the food industry to stabilize emulsions, and they appear as promising candidates in the pharmaceutical field too. All proteins and some polysaccharides are able to adsorb at a globule surface, thus decreasing the interfacial tension and enhancing the interfacial elasticity. However, most polysaccharides stabilize emulsions simply by increasing the viscosity of the continuous phase. Proteins and polysaccharides may also be associated either through covalent bonding or electrostatic interactions. The combination of the properties of these biopolymers under appropriate conditions leads to increased emulsion stability. Alternative layers of oppositely charged biopolymers can also be formed around the globules to obtain multi-layered "membranes". These layers can provide electrostatic and steric stabilization thus improving thermal stability and resistance to external treatment. The novel biopolymer-stabilized emulsions have a great potential in the pharmaceutical field for encapsulation, controlled digestion, and targeted release although several challenging issues such as storage and bacteriological concerns still need to be addressed.

This study investigated the in vitro release of vancomycin, gentamicin, and lidocaine from novel electrospun sandwich-structured polylactide-polyglycolide (PLGA)/collagen nanofibrous membranes. For the electrospinning of biodegradable membranes, PLGA/collagen and PLGA/vancomycin/gentamicin/lidocaine were separately dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP). They were then electrospun into sandwich structured membranes, with PLGA/collagen for the surface layers and PLGA/drugs for the core layer. After electrospinning, an elution method and HPLC assay were employed to characterize the in vitro release rates of the pharmaceutics over a 30-day period. The experiment showed that biodegradable nanofibrous membranes released high concentrations of vancomycin and gentamicin (well above the minimum inhibition concentration) for 4 and 3 weeks, respectively, and lidocaine for 2 weeks. A bacterial inhibition test was carried out to determine the relative activity of the released antibiotics. The bioactivity of vancomycin and gentamicin ranged from 30% to 100% and 37% to 100%, respectively. In addition, results indicated that the nanofibrous membranes were functionally active in responses in human fibroblasts. By adopting the electrospinning technique, we will be able to manufacture biodegradable biomimetic nanofibrous extracellular membranes for long-term drug delivery of various pharmaceuticals.

In this article, silk fibroin particles with average diameter of 980 nm were fabricated via self assembly. Exceptional loading efficiency and release patterns of hydrophobic and protein drugs were observed. Furthermore, smoother release patterns were observed with increase loading of the hydrophobic and protein model drugs, only about 23% FITC–BSA and 34% RhB were released from the silk particles at their highest corresponding loading in 50 days. Most importantly, osteoblasts’ viability was augmented during co-culture with silk fibroin particles, as shown by Alamar Blue assay. Attachment of the particles and delivery of model drugs to cells were confirmed by fluorescence images and flow cytometry. Hence, the silk fibroin particles could be potential biomaterial for application in controlled release and pharmaceutics.

Lutein is a well known antioxidant and anti-free radical used in cosmetic, nutraceutical industry with potential application in pharmaceutics as supportive antioxidant in treatments. As lipophilic molecule it is poorly soluble in water and has a low bioavailability. Lutein nanosuspension was prepared to enhance dissolution velocity, saturation solubility (C(s)), which are major factors determining oral bioavailability and penetration into the skin. High pressure homogenization (HPH) was used to prepare lutein nanosuspension. Particle size was determined by photon correlation spectroscopy (PCS) and laser diffractometry (LD). The lowest PCS diameter obtained was about 429 nm, the LD diameter 90% of 1.2 μm. The zeta potential was about -40 mV in water and -17 mV in the original dispersion medium. The 3 month storage study at different temperatures (4°C, 25°C, 40°C) confirmed physical stability despite the low zeta potential of -17 mV in original surfactant solution. A pronounced increase in saturation solubility by 26.3 fold was obtained for lutein nanocrystals compared to coarse powder. The lutein nanosuspension was converted into pellets and filled into hard gelatin capsules for nutraceutical use, showed a superior in vitro release (factor of 3-4). Lyophilized nanosuspension was prepared for subsequent incorporation into creams and gels. The lyophilized nanosuspension was very well re-dispersible (435 nm). Using cellulose nitrate membranes as in vitro model, permeation through this barrier was 14× higher for lutein nanocrystals compared to coarse powder. However, pig ear skin did not allow lutein to permeate but supported localization of the lutein in the skin where it should act anti-oxidatively.

We provide an overview of latent variable methods used in pharmaceutics and integrated with advanced characterization techniques such as vibrational spectroscopy. The basics of the most common latent variable methods, principal component analysis (PCA), principal component regression (PCR) and partial least-squares (PLS) regression, are presented. Multiple linear regression (MLR) and methods for improved interpretation, variable selection, classification and validation are also briefly discussed. Extensive use of the methods is demonstrated by compilation of the recent literature.

With the rapid development of nanotechnology, there is a growing interest on the application of nanoparticles in various fields such as photonics, catalysis, magnetics, and biotechnology including cosmetics, pharmaceutics, and medicines. However, little is known about their potential toxicity to human health. Owing to their special properties, nanoparticles have the capacity to bypass the blood-brain barrier (BBB). However, the toxic effects of nanoparticles on central nervous system (CNS) function are still lacking. And the interactions of nanoparticles with the cells and tissues in CNS are poorly understood. Thus, neurotoxicity induced by nanoparticles is still a new topic that requires more attention. In this review, we summarized the pathways by which the nanoparticles could enter into the CNS and the recent investigations on the neurotoxicity of nanoparticles both in vitro and in vivo, as well as the potential mechanisms. Furthermore, the future direction in the neurotoxicity studies of nanoparticles is also discussed.

Solid lipid nanoparticles (SLN) are distinguishable from nanostructured lipid carriers (NLC) by the composition of the solid particle matrix. Both are an alternative carrier system to liposomes and emulsions. This review paper focuses on lipid nanoparticles for dermal application. Production of lipid nanoparticles and final products containing lipid nanoparticles is feasible by well-established production methods. SLN and NLC exhibit many features for dermal application of cosmetics and pharmaceutics, i.e. controlled release of actives, drug targeting, occlusion and associated with it penetration enhancement and increase of skin hydration. Due to the production of lipid nanoparticles from physiological and/or biodegradable lipids, this carrier system exhibits an excellent tolerability. The lipid nanoparticles are a "nanosafe" carrier. Furthermore, an overview of the cosmetic products currently on the market is given and the improvement of the benefit/risk ratio of the topical therapy is shown.

Three-dimensional printing includes a wide variety of manufacturing techniques, which are all based on digitally-controlled depositing of materials (layer-by-layer) to create freeform geometries. Therefore, three-dimensional printing processes are commonly associated with freeform fabrication techniques. For years, these methods were extensively used in the field of biomanufacturing (especially for bone and tissue engineering) to produce sophisticated and tailor-made scaffolds from patient scans. This paper aims to review the processes that can be used in pharmaceutics, including the parameters to be controlled. In practice, it not straightforward for a formulator to be aware of the various technical advances made in this field, which is gaining more and more interest. Thus, a particular aim of this review is to give an overview on the pragmatic tools, which can be used for designing customized drug delivery systems using 3D printing.